• 1.

    Perkovic V, et al. Management of patients with diabetes and CKD: Conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int 2016; 90:11751183.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Davies MJ, et al. Management of hyperglycemia in type 2 diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41:26692701.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    de Boer IH. The expanding resume of SGLT2 inhibitors. Lancet Diabetes Endocrinol 2019; 7:585587.

  • 4.

    Perkovic V, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380:22952306.

  • 5.

    Tuttle KR. SGLT2 inhibitor and incretin mimetic therapy for type 2 diabetes and chronic kidney disease. Lancet Diabetes Endocrinol 2019; 7:414415.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    American Diabetes Association. 7. Diabetes Technology: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019; 42 [Suppl 1]:S71–S80.

    • Search Google Scholar
    • Export Citation

Diabetes and CKD: New Approaches to Managing a Common Condition

  • 1 Ian H. de Boer, MD, MS, is Professor of Medicine in the Division of Nephrology and Associate Director of the Kidney Research Institute at the University of Washington, Seattle, USA.
Full access

Diabetes treatment has advanced rapidly over the past decade, with new drugs and technologies developed and translated into clinical care. Many of these treatments affect the kidney, are affected by chronic kidney disease (CKD), or carry both effects. In addition, new data have been published on foundational elements of care for people with diabetes and CKD, including lifestyle, ascertainment of glycemia, glycemic targets, and use of renin-angiotensin system (RAS) inhibitors. Providers and patients rightly ask how to apply the new treatments and integrate them into tailored existing care paradigms.

KDIGO has initiated a new clinical practice guideline to help guide medical management for people with diabetes and CKD. The goal of the new clinical practice guideline is to provide evidence-based recommendations for the care of people with diabetes and CKD. The guideline arose from a KDIGO Controversies Conference held in 2015 that outlined critical areas in need of evidence-based recommendations (1). The scope of the guideline was then refined by the KDIGO diabetes and CKD guideline writing group, with input through open commentary from the broad community engaged in managing diabetes and CKD.

The new guideline will take a comprehensive approach, covering lifestyle, glycemia assessment and targets, use of medications that target both glycemia and other intermediate targets, self-management, and systems of care (see box). The guideline is designed to apply to people with diabetes and any stage of CKD, from elevated urine albumin excretion and normal estimated GFR (eGFR) to severely reduced eGFR to ESKD treated with dialysis or kidney transplantation, highlighting the aspects of care that are common across the CKD spectrum and also those that should differ by severity of CKD. Similarly, the guideline will address care for people with both type 1 and type 2 diabetes, highlighting common and differential approaches where appropriate. The guideline will be informed by a systematic literature review performed by an expert evidence review team, focusing on high-level evidence from clinical trials.

New drugs will be addressed by this new diabetes and CKD guideline. Three new classes of drugs are revolutionizing diabetes care: sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors (2). All three classes reduce blood glucose, with a low risk of hypoglycemia. In addition, SGLT2 inhibitors and GLP-1 receptor agonists have shown substantial benefits in terms of cardiovascular and kidney outcomes (Table 1). These benefits were first demonstrated in large cardiovascular outcomes trials that were mandated by regulatory agencies to ensure cardiovascular safety of new diabetes drugs. SGLT2 inhibitors and GLP-1 receptor agonists proved to be not only safe but beneficial. In each of these drug classes, several specific drugs reduced cardiovascular events in high-risk populations (2). SGLT2 inhibitors also substantially reduced GFR loss in secondary analyses (3)—an effect confirmed in the recent CREDENCE trial (4). GLP-1 receptor agonists may also have renal benefits (5). However, all of these drugs do have adverse effects, most are restricted below certain eGFR thresholds and in kidney failure, and combinations with other glucose-lowering drugs remain poorly developed (3). Therefore, further guidance is needed on the implementation of these promising new drugs in clinical nephrology practice.

Table 1.

Summary of the benefits and harms of SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors, by class, as observed in large, placebo-controlled clinical outcomes trials

Table 1.

Key questions to be addressed by the new KDIGO guideline on diabetes and CKD

  1. Do lifestyle interventions (exercise/physical activity, and smoking cessation) versus usual care improve clinically relevant outcomes and intermediate outcomes and reduce clinically relevant harms?

  2. Do dietary interventions (caloric restriction diet, low-potassium diet, low-sodium diet, low-phosphate diet, low-protein diet and whole food diets) versus usual diet improve clinically relevant outcomes and intermediate outcomes and reduce clinically relevant harms?

  3. What is the equivalency of HbA1c compared with freqently measured blood glucose (continuous glucose monitoring or mutiple capillary blood glucose measurements)?

  4. Compared with blood glucose monitoring and/or HbA1c determination, do alternative biomarkers (glycated albumin, fructosamine) improve clinically relevant outcomes and decrease clinically relevant harms?

  5. Compared with HbA1c determination, does blood glucose monitoring (continuous interstitial glucose monitoring, self-monitoring blood glucose) improve clinically relevant outcomes and decrease harms?

  6. Does reducing blood glucose to a lower versus higher target improve clinically relevant outcomes and intermediate outcomes, and reduce clinically relevant harms?

  7. What are the most effective education, self-management, and healthcare delivery programs to improve clinically relevant and intermediate outcomes, and reduce clinically relevant harms?

  8. What are the effects of metformin on clinically relevant outcomes, intermediate outcomes, and clinically relevant harms?

  9. What are the effects of other glucose-lowering medications (sulfonylureas, thiazolidinediones, α-glucosidase inhibitors, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, insulin) on clinically relevant outcomes, intermediate outcomes, and clinically relevant harms?

  10. Do renin-angiotensin system (RAS) inhibtors improve clinically relevant outcomes and intermediate outcomes, and reduce clinically relevant harms?

  11. Does dual RAS inhibition compared with single RAS inhibition improve clinically relevant outcomes and intermediate outcomes, and reduce clinically relevant harms?

  12. Does the addition of a medication blocking the production or action of aldosterone to RAS inhibitors compared with RAS inhibition alone improve clinically relevant outcomes and intermediate outcomes, and reduce clinically relevant harms?

Technology has also advanced in diabetes care. In particular, continuous glucose monitoring is facilitating more intensive glycemic control, particularly in type 1 diabetes (6). New biomarkers, such as glycated albumin and fructosamine, have also been proposed to assess glycemia in CKD, because hemoglobin A1c may be biased or imprecise when red blood cell turnover increases with low eGFR and the use of erythropoietin-stimulating agents.

Of course, new drugs and technologies cannot treat diabetes and CKD on their own. These new treatments must be added to and integrated with established therapies, including lifestyle interventions and proven therapies, such as metformin and RAS inhibitors. Of lifestyle interventions, dietary sodium, dietary protein, and physical activity have been best studied. All treatments must be applied in a manner that engages and is acceptable to patients and is delivered in care models that acknowledge local patterns of care and local resources. Importantly, diabetes has grown most rapidly in low-income countries. Treatment paradigms must take into account the cultural values and resources of diverse contexts.

The care of people with diabetes and CKD makes large demands on patients and is necessarily multidisciplinary in nature. Effective guidelines must therefore reflect patient priorities and the perspectives of multiple approaches to care. Such guidelines must also acknowledge and account for the large range of care settings across the world. For these reasons, the KDIGO diabetes and CKD guideline writing group includes patients along with members from diverse professional backgrounds (nephrology, endocrinology, primary care, cardiology, pharmacology, nutrition) and from across the globe (United States, United Kingdom, Netherlands, Germany, India, Nigeria, Singapore, Hong Kong, and Brazil). It is anticipated that KDIGO and this writing group will release a draft set of recommendations for public commentary in December 2019, with a final guideline published in early 2020.

References

  • 1.

    Perkovic V, et al. Management of patients with diabetes and CKD: Conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int 2016; 90:11751183.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Davies MJ, et al. Management of hyperglycemia in type 2 diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41:26692701.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    de Boer IH. The expanding resume of SGLT2 inhibitors. Lancet Diabetes Endocrinol 2019; 7:585587.

  • 4.

    Perkovic V, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380:22952306.

  • 5.

    Tuttle KR. SGLT2 inhibitor and incretin mimetic therapy for type 2 diabetes and chronic kidney disease. Lancet Diabetes Endocrinol 2019; 7:414415.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    American Diabetes Association. 7. Diabetes Technology: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019; 42 [Suppl 1]:S71–S80.

    • Search Google Scholar
    • Export Citation
Save